Bexarotene (Bex) is a FDA-approved drug used to treat cutaneous T-cell lymphoma (CTCL). It binds with high affinity to the retinoid-X-receptor (RXR), a nuclear receptor implicated in numerous biological pathways. Bex may have the potential to attenuate estrogenic activity by acting as an estrogen receptor alpha (ERα) signaling antagonist, and…
Bexarotene (Bex) is a FDA-approved drug used to treat cutaneous T-cell lymphoma (CTCL). It binds with high affinity to the retinoid-X-receptor (RXR), a nuclear receptor implicated in numerous biological pathways. Bex may have the potential to attenuate estrogenic activity by acting as an estrogen receptor alpha (ERα) signaling antagonist, and can therefore be used to treat ERα-positive cancers, such as breast cancer. Using dual luciferase reporter assays, real-time qRT-PCR, and metabolic proliferation assays, the anti-estrogenic properties of Bex were ascertained. However, since Bex produces numerous contraindications, select novel RXR drug analogs were also evaluated. Results revealed that, in luciferase assays, Bex could significantly (P < 0.01) inhibit the transcriptional activity of ERα, so much so that it rivaled ER pan-antagonist ZK164015 in potency. Bex was also able to suppress the proliferation of two breast cancer cell models, MCF-7 and T-47D, and downregulate the expression of an estrogen receptor target gene (A-myb), which is responsible for cell proliferation. In addition, novel analogs A30, A33, A35, and A38 were evaluated as being more potent at inhibiting ERE-mediated transcription than Bex at lower concentrations. Analogs A34 and A35 were able to suppress MCF-7 cell proliferation to a degree comparable to that of Bex. Inhibition of T-47D cell proliferation, by contrast, was best achieved by analogs A34 and A36. For those with ERα – positive breast cancer who are refractory to current chemotherapeutics used to treat breast cancer, Bex and its analogs may prove to be useful alternative options.
Aristotle studied developing organisms, among other things, in ancient Greece, and his writings shaped Western philosophy and natural science for greater than two thousand years. He spent much of his life in Greece and studied with Plato at Plato's Academy in Athens, where he later established his own school called…
Aristotle studied developing organisms, among other things, in ancient Greece, and his writings shaped Western philosophy and natural science for greater than two thousand years. He spent much of his life in Greece and studied with Plato at Plato's Academy in Athens, where he later established his own school called the Lyceum. Aristotle wrote greater than 150 treatises on subjects ranging from aesthetics, politics, ethics, and natural philosophy, which include physics and biology. Less than fifty of Aristotle's treatises persisted into the twenty-first century. In natural philosophy, later called natural science, Aristotle established methods for investigation and reasoning and provided a theory on how embryos generate and develop. He originated the theory that an organism develops gradually from undifferentiated material, later called epigenesis.
